Signal transducers and activators of transcription (STAT) family proteins transduce pivotal biological effects of various cytokines and hormones. STAT3 proteins are known to play a central role in the regulation of growth, differentiation, and survival of many types of cells. However, the function of STAT3 in myogenesis still remains largely unknown. We now provided direct evidence that STAT3 could induce myogenic differentiation and this effect might be mediated by interaction with MyoD--the essential transcription factor during myogenic differentiation. Furthermore, leukemia inhibitory factor (LIF) might be the upstream factor which activated JAK2/STAT3 pathway to stimulate muscle cell differentiation. Taken together, these results provide a molecular basis for further understanding of the muscle regeneration mechanism.